Lodestone Biomedical’s Immunotherapy Response Indication System (IRIS) interrogates the binding states of functionalized magnetic nanoparticles (fMNPs) localized in biosensor probes for direct in vivo longitudinal monitoring of therapeutic responses in the patient tumor immune microenvironment (TIME). Herein, we propose to commercialize the IRIS platform technology for pharmacotyping immunotherapies and temozolomide (TMZ) in glioblastoma multiforme (GBM) brain tumors. IRIS technology offers the potential for direct in vivo pharmacotyping capable of differentiating phenotypic responses across ultimately numerous tumor-derived oncogenic and immunogenic factors. This Phase 1 project directly validates the IRIS platform device measurements of target binding sensitivity to singleplex fMNP pairs in solution vs standard ELISA via Bland-Altman plot analysis, with a go-no-go requirement for >95% CI. The potential for IRIS platform technology will be demonstrated across a restricted subset of target specific biosensors in the well- characterized GBM model system, as well as appropriately pharmacotyping responsiveness to TMZ in more diverse MGMT positive and negative patient derived tumor lines. Finally, preliminary investigations of safety and proof of concept will be demonstrated in real time, localized, in vivo GBM pharmacotyping of combination therapy. Ultimately, IRIS technology will bring reliable indicators of therapeutic responsiveness with a practical implementation to the patient bedside.